Can you elaborate a little more?
Are you using the stock front end or LaunchBox?
Are you using the stock Replay controllers or something different?
If you are have you plugged in a USB dongle for each Replay controller?
If yes try pairing one at a time. Plug in one dongle, hold the first controller near the Replay, and double tap the middle button. This should light the top left light. Do the same same for the next one. This second one should light top left.

If you have gotten this far are are still having issue the next thing would try is to make sure the controllers inputs are set up correctly. To be extra sure that they map correctly plug in a mouse to the Replay. In the Windows System Tray close out the virtual mouse application, and then map the controllers.

What game are you trying to play? if it is a system that uses MAME you may need to plug in a keyboard,launch the game in question, press TAB on the keyboard, and then configure the inputs directly in the MAME emulator.

If you are having a software problem be it front end, Windows, or want to try RetroArch and LauchBox but need help feel free to contact me. Post on the forum, PM here, or on Discord. I will be more then happy to do my best to get you sorted.

Im not very good with computers. I have the stock dreamcade controllers and have tried plugging it in the dreamcade while the game was on. We are trying to play tmnt for super Nintendo.
I will try to use the keyboard to get to the options

WheatPasta is correct. If you are still having issues with one if the controllers pairing. You may have an issue with either the dongle or the controller. This will require contacting Dreamcade for a replacement.

If both controllers are syncing to their respective dongle. Type joy.cpl at the bottom of the search box on desktop. This will prompt a window to test both controllers.
If your playing on SNES, hit escape on the keyboard. A submenu on top will appear as the window appears. Use this to make internal changes to the actual emulator. Or even bind the controllers for a more response.